This project is concerned with human biochemical genetics in the study of the biochemical manifestations of heritable disease. It is devoted to the detection and definition of new metabolic diseases and to the study of metabolic interrelations in these and other metabolic disorders. These interrelations of intermediary metabolism are related to the pathogenesis of the clinical manifestations of these diseases. They relate particularly to the development of central nervous system function and to aberrations in this developmental process. It is through studies in this area that methods of treatment for some of these diseases may be developed. This laboratory has been involved in recent years in the definition of two previously unrecognized inborn errors of metabolism. These are hyperglycinemia and hyperuricemia with hypoxanthine-guanine phosphoribosyl transferase deficiency. Both of these appear to be of genetic and metabolic interest. Studies on both diseases are in progress. Similar studies are in progress on other metabolic disorders. The search for other new metabolic diseases is also actively being pursued.